Children's National Hospital Washington, DC, District of Columbia, United States
Background/Case Studies: Monoclonal antibody therapies, such as Daratumumab, are used to treat various cancers, including multiple myeloma. Daratumumab targets CD38, a protein highly expressed on myeloma cells but also present on red blood cells. As a result, patients receiving Daratumumab often show panreactivity in Indirect Antiglobulin Tests (IAT), which can obscure clinically significant alloantibodies. While solutions like red cell treatment with dithiothreitol (DTT) or proteolytic enzyme (trypsin, papain) exist, they have limitations in detecting certain alloantibodies. This study aimed to evaluate a novel anti-idiotypic reagent (from Bio-Rad Laboratories – not yet commercialized) for its ability to neutralize Daratumumab interference in pretransfusion testing and as a possible alternative to existing testing solutions.
Study
Design/Methods: The anti-idiotypic anti-daratumumab was provided ready-to-use. A total of sixteen pediatric samples, previously resolved using DTT-treated red blood cells, were included in the evaluation. All these patients were recently transfused (< 1 month) and received their daratumumab infusion within the past 3 months. Reaction strengths in gel cards resulting from Daratumumab interference were recorded. Initial testing was performed using a 10% (v/v) concentration of the neutralizing solution. If complete neutralization was not achieved, the concentration was increased to 30%. No pre-incubation was required; testing was conducted immediately after adding the neutralizing solution.
Results/Findings: Patient age ranged between 13 to 16 years old and the last infusion of daratumumab was in average 49 days ago (range 35 to 83 days). All sixteen samples exhibited panreactivity in the IAT gel card using a three-cell screening panel, with reaction strengths ranging from 1+ to 2+. Reaction strengths were consistent across all red blood cells (RBC) but one cell which was not reacting with one sample. After addition of 10% (v/v) complete neutralization was achieved in 8 cases. The 8 other samples were efficiently neutralized using the 30% protocol (20% protocol was not tested due to limited availability of the reagent). There was no significant difference in term of daratumumab infusion date between each group: 47 days for the 10% group and 50 days for the 30% group (p: 0.35). Overall, 100% samples were neutralized without impact on the turnaround time.
Conclusions: This anti-idiotypic anti-Daratumumab antibody demonstrated highly efficient neutralization. All samples, regardless of the date of the last Daratumumab infusion, were effectively neutralized using either the 10% or 30% protocol. This user-friendly reagent can become a new candidate for Daratumumab neutralization in pre transfusion testing.
